Type 1 Diabetes: Its Problems and Solutions

Formerly known as juvenile-onset diabetes, type 1 diabetes (T1D) is an endocrine disorder characterized by hyperglycemia due to insulin deficiency.¹ Most cases of T1D are immune-mediated due to cellular-mediated autoimmune destruction of beta cells, resulting in inadequate insulin secretion and hyperglycemia via abnormal macronutrient metabolism.^1,2 Acute hyperglycemia can cause metabolic emergencies such as diabetic ketoacidosis (DKA) and a hyperosmolar hyperglycemic state. Chronic hyperglycemia can cause vascular complications such as nephropathy, retinopathy, and cardiovascular disease.

EPIDEMIOLOGY

According to the American Diabetes Association (ADA), immune-mediated T1D accounts for 5% to 10% of diabetes cases. Although T1D may occur at any age, 50% to 60% of patients with T1D present at 16 years and younger.^3-5 In a population- based cross-sectional study of children and adolescents in 2009, the overall prevalence of newly diagnosed cases of T1D was 1.93 per 1000 patients (95% CI, 1.88-1.97), with whites having the highest incidence of newly diagnosed T1D.⁶

RISK FACTORS

A patient’s genome is a significant risk factor for T1D, as a case-control study of approximately 8000 patients with T1D identified 7 genetic variants associated with an increased risk of T1D and celiac disease.⁷ Other possible risk factors associated with an increased risk of T1D include high birth weight, childhood obesity, and a higher maternal age at birth.^8-11 Childhood immunizations, however, are not associated with an increased risk for T1D.^12,13 Conditions complicated by T1D include celiac disease and increased risk of hip fracture.^14,15

HISTORY AND PHYSICAL

Patients with T1D rarely present asymptomatically; the most common symptoms include polyuria and nocturia, enuresis, lethargy, fatigue, polyphagia, and abdominal pain.⁴ Approximately 30% of children and adolescents with newly diagnosed T1D may present with DKA.¹⁶ When obtaining a patient’s medical history, ask about autoimmune diseases and a family history of diabetes.^3,5 If a patient presents with an autoimmune disease, evaluate whether associated symptoms are present.

It is important to document the patient’s weight, as recent sudden weight loss is common in T1D.^1,4 Additionally, patients may present with skin conditions associated with T1D, such as diabetic blisters.¹⁷ In the extremities, patients may present with diabetic foot ulcers or loss of sensation and reflex.³

DIAGNOSIS

The 2016 ADA guidelines list the criteria for diagnosing diabetes, which include the presence of at least 1 of the following³:

• Fasting blood glucose level ≥126 mg/dL
• Two-hour blood glucose level ≥200 mg/dL during a 75-g oral glucose tolerance test
• Glycated hemoglobin (A1C) level ≥6.5%
• In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random blood glucose level ≥200 mg/dL

The ADA guidelines recommend that clinicians use blood glucose levels instead of A1C levels to diagnose acute T1D in individuals with hyperglycemia symptoms (ie, polydipsia, polyphagia, polyuria; ADA grade E).³ Additional parameters (eg, electrolytes, blood urea nitrogen, creatinine, arterial blood gas, serum or urine ketones) should be tested to determine DKA severity (Table 1).¹⁸ The ADA guidelines also recommend screening for thyroid disease and celiac disease soon after diagnosing T1D in children (ADA grade E). In patients 10 years and older, obtaining a fasting lipid profile after a T1D diagnosis is recommended (ADA grade E).^3,5

Urine studies should also be performed. If DKA is suspected, urinalysis and urine ketone testing via the dipstick method are recommended; if an infection is suspected, urinalysis is recommended. The ADA and the National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend conducting annual albuminuria screening starting 5 years after a T1D diagnosis.^3,19

PROGNOSIS

Metabolic Complications

In pediatric patients with T1D, the mortality rates associated with DKA are 0.15% to 0.3% in national population-based studies.²⁰ A prospective cohort study of 1243 children 19 years and younger with T1D noted that severe hypoglycemia occurs in 19 per 100 person-years.²¹

Vascular Complications

In addition to the microvascular complications of T1D (ie, retinopathy, nephropathy, and neuropathy), patients may be at risk for macrovascular complications.^22-25 For example, a systematic review of patients with diabetes (but without acute foot ulcerations or previous history of amputation) noted that in patients with T1D, there was an 18% increased risk of amputation for each 1% increase in A1C level.²⁶

Infectious Complications

T1D is associated with several infections, such as malignant otitis externa, hepatitis B, and hepatitis C (Table 2). Additionally, pediatric patients with T1D may be prone to vulvovaginal candidiasis, as observed in a case-control study of 35 girls. This study also identified that a higher mean A1C level was associated with a diagnosis of vulvovaginal candidiasis.²⁷

Neurologic Complications

In pediatric patients with T1D, early-onset diabetes and hypoglycemia were associated with poorer cognitive performance.²⁸ In a study that compared 244 children with diabetes with 110 siblings and 209 classmates, T1D was associated with increased behavior concerns reported by parents, but not academic performance.²⁹

Mortality

Compared with the general population, T1D was associated with increased all-cause and cardiovascular mortality.³⁰ Additionally, a cohort study from Scotland found that after 20 years of age, life expectancy may decrease by about 12 years in patients with T1D compared with the general population.³¹ One retrospective cohort study that evaluated patients with a diagnosis of T1D during childhood found that an increased risk of death in early adulthood was associated with higher mean pediatric A1C levels and a history of severe hypoglycemia episodes.³²

Rehospitalization

In a survey of 535 patients given a diagnosis of diabetes before 18 years of age, 46% of respondents reported rehospitalization.³³

TREATMENT

The ADA guidelines recommend treating T1D with daily subcutaneous insulin therapy consisting of 3 or 4 daily injections of basal and prandial insulin to counteract insulin depletion (ADA grade A); insulin formulations vary in their pharmacokinetic action (Table 3).³ The total daily insulin doses depend on age, weight, pubertal status, medical history, and physical activity.³⁴ Insulin regimens for patients with T1D are either a split/mixed regimen or a basal/bolus regimen.³ The split/mixed regimen consists of 2 or 3 daily insulin injections given in combination with multiple insulins, whereas the basal/bolus regimen consists of a long-acting insulin and preprandial insulin injections.

Table 3. Insulin Types and Pharmacokinetic Parameters³⁴

Insulin Type

Brand (generic)

Pharmacokinetics

Onset of Action

Peak of Action

Duration of Action (hr)

Rapid-acting

Novolog (aspart insulin)

Humalog (lispro insulin)

Apidra (glulisine insulin)

10-15 min

30-90 min

3-4

Short-acting

Novolin-R (regular insulin)

Humulin-R (regular insulin)

30-60 min

2-4 hr

4-6

Intermediate-acting

Novolin-N (NPH insulin)

Humulin-N (NPH insulin)

1-2 hr

3-10 hr

8-15

Long-acting

Lantus (insulin glargine)

2-4 hr

No peak

20-24

Levemir (insulin detemir)

1-2 hr

6-12 hr

6-24

Subcutaneous insulin can be injected in multiple sites (Figure). It is important to counsel patients and caregivers to ensure rotation of insulin injection sections. If a mixed regimen is used, instruct the patient/caregiver to draw up the regular-acting insulin first (clear appearance) in the syringe, followed by the intermediate-acting insulin (cloudy appearance).

The adverse effects of insulin include injection-site reactions, hypoglycemia, hypokalemia, and weight gain. It is important for patients with T1D and caregivers to identify signs and symptoms of hypoglycemia (eg, cognitive impairment, loss of consciousness, seizure, coma) and treatment options (eg, glucose/carbohydrate- containing foods, glucagon).³

MANAGEMENT

Glycemic goals should be individualized to achieve proper glycemic control, minimize the risk of hypoglycemia, and maintain normal growth and development. In children, the recommended goals are A1C levels less than 7.5% (ADA grade E), preprandial glucose levels between 90 and 130 mg/dL, and bedtime or overnight glucose levels between 90 and 150 mg/dL.³ Lifestyle interventions include dietary recommendations (ADA grade A), physical activity for at least 60 minutes per day in children (ADA grade B), and individualized diabetes self-management education for patients and caregivers (ADA grade B).³

ROLE OF THE PHARMACIST

Pharmacists can administer immunizations to pediatric patients with T1D based on the recommended schedule set forth by the Advisory Committee on Immunization Practices guidelines (ADA grade C). ^3,5 It is important to ensure that patients with T1D receive the influenza vaccine but to exercise caution if administering the live-attenuated influenza vaccine in pediatric patients with T1D and chronic conditions, because administration of the live vaccine may worsen a patient’s chronic conditions, including T1D.³⁵

Patients and caregivers should receive appropriate, individualized diabetes self-management education and support (ADA grade B).³ Pharmacists may also play a key role in initial patient counseling, as initial diabetes education in outpatient settings, compared with inpatient education in children with new-onset T1D, is associated with long-term glycemic control and similar acute complication rates (level 2 evidence).³⁶ All pediatric patients with T1D should be advised not to smoke or use tobacco products (ADA grade A); if patients/caregivers do smoke, smoking cessation should be included in therapy management (ADA grade B).³ The ADA also set forth quarterly and annual routine follow-up recommendations for pediatric patients with T1D (Table 4).⁵ A retrospective cohort study found that pediatric patients with T1D and a history of smoking had increased A1C levels, diastolic blood pressure, triglyceride levels, and total cholesterol levels.³⁷ Transition of care from pediatric clinicians to adult clinicians decreased hospitalization risk.³⁸

Brian J. Catton, PharmD, graduated from the Bernard J. Dunn School of Pharmacy at Shenandoah University in Winchester, Virginia, in 2010. He received the Distinguished Young Pharmacist Award from the New Jersey Pharmacists Association in 2014. He currently is a Pharmacist Communicator at Ashfield Healthcare in Ivyland, Pennsylvania. His areas of interest include pediatrics, immunizations, drug-therapy management, social media, patient counseling, and immuno-oncology.

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